title: Peroxynitrite aggravates myocardial reperfusion injury in the isolated perfused rat heart.
abstract: OBJECTIVE
  This study examined the effects of peroxynitrite (ONOO-) on cardiac function and cellular injury following ischemia (30 min) and reperfusion (60 min) in isolated perfused rat hearts.
  
  
  METHODS
  3-Morpholinosydnonimine (SIN-1, 0.1 mM), an ONOO- donor, was administered alone or combined with superoxide dismutase (SOD, 300 U/ml) or glutathione (GSH, 1 mM) at the time of reperfusion.
  
  
  RESULTS
  Administration of SIN-1 alone significantly aggravated post-ischemic myocardial injury characterized by depressed cardiac function recovery (p < 0.05 vs. vehicle), increased lactic dehydrogenase (LDH) and creatine kinase (CK) release (p < 0.01 vs. vehicle), and enlarged necrotic size (p < 0.01 vs. vehicle). The co-administration of either SOD to decrease the formation of ONOO-, or GSH to increase the detoxification of ONOO-, completely blocked the detrimental effects of SIN-1 and exerted significant cardioprotective effects against reperfusion injury.
  
  
  CONCLUSIONS
  These results suggest that ONOO- may play a significant role in postischemic myocardial injury.
authors.affiliation: Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107-5004, USA.
authors.forename: X L
authors.initials: XL
authors.lastname: Ma
authors.forename: B L
authors.initials: BL
authors.lastname: Lopez
authors.forename: G L
authors.initials: GL
authors.lastname: Liu
authors.forename: T A
authors.initials: TA
authors.lastname: Christopher
authors.forename: H
authors.initials: H
authors.lastname: Ischiropoulos
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D009206:Myocardium / Q000201:enzymology; D009566:Nitrates / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D009566:Nitrates; D014665:Vasodilator Agents; C039642:peroxynitric acid; C002385:linsidomine; D008981:Molsidomine; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005978:Glutathione